On June 6, 2022 The Menarini Group ("Menarini") and Radius Health, Inc. ("Radius") (NASDAQ: RDUS) (collectively, the "Companies") reported the presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting of data from the EMERALD phase 3 clinical trial (NCT03778931) (Press release, Menarini, JUN 6, 2022, View Source [SID1234615669]). In a non-pre-specified subgroup analysis of patients with ER+/HER2− metastatic breast cancer (mBC) without prior chemotherapy in the metastatic setting, elacestrant significantly prolonged progression-free survival (PFS) compared to standard of care (SOC) endocrine therapy.

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EMERALD study met both of its pre-specified primary end points of progression-free survival (PFS) in the overall population and in patients with ESR1 mutation (mESR1).1

77.8% (n=371) out of the 477 patients enrolled in the trial had not received prior chemotherapy in the metastatic setting for ER+/HER2−mBC. Among these patients, elacestrant showed the following results compared to SOC:
– 31% reduction in the risk of progression or death in all patients (HR=0.681 [95% CI: 0.520 – 0.891]; P=0.00388) and prolonged median PFS (3.68 vs 1.97 months).
– 46% reduction in the risk of progression or death in patients with mESR1 (HR=0.535 [95% CI: 0.356 – 0.799]; P=0.00235) and prolonged median PFS (5.32 vs 1.91 months).

At 6 months, PFS rate with elacestrant was 38.18% vs. 23.47% with SOC in the overall population, and 43.79% vs. 23.83% in the ESR1 mutation population.

PFS rate at 12 months with elacestrant was 27.12% vs. 12.19% with SOC in the overall population, and 31.48% vs. 12.36% in the ESR1 mutation population.

In exploratory subgroup analyses, elacestrant significantly reduced the risk of progression or death and prolonged median PFS vs fulvestrant in all patients without prior chemotherapy (HR=0.636 [95% CI: 0.465-0.868]; median PFS 3.68 vs 1.97 months; P=0.0032), and in patients with mESR1 without prior chemotherapy (HR=0.487 (95% CI: 0.310-0.761; median PFS 5.32 vs 1.91 months; P=0.0015).

Elacestrant had a manageable safety profile in patients without prior chemotherapy consistent with the overall population.1

Dr. Virginia Kaklamani, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center, commented, "Elacestrant is a potential exciting new endocrine therapy after progression on a CDK4/6 inhibitor in women with ER+ metastatic breast cancer. The EMERALD trial showed that elacestrant is active even in patients whose tumors harbor an ESR1 mutation. This subset analysis additionally showed that patients who have not previously been treated with chemotherapy in the metastatic setting had longer progression free survival up to 5.32 months."

Menarini plans to pursue combination studies and study the potential of elacestrant to be effective in addressing the highest unmet needs for ER+/HER2-patients.

Poster Presentation: 477

Abstract Title: Subgroup analysis of patients with no prior chemotherapy in EMERALD: A phase 3 trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC)

Abstract Number: 1100

Poster Session: Breast Cancer – Metastatic

About Elacestrant (RAD1901) and EMERALD Phase 3 Study

Elacestrant is an investigational selective estrogen receptor degrader (SERD), out-licensed to Menarini Group, which is being evaluated for potential use as a once daily oral treatment in patients with ER+/ HER2- advanced breast cancer. In 2018, elacestrant received fast track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+/HER2- advanced/metastatic breast cancer patients. The study enrolled 477 patients who have received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoint of the study was progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR).

References

1. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 May 18:JCO2200338. doi.org: 10.1200/JCO.22.00338. Epub ahead of print.